Abstract
A critical component in the interpretation of systems-level studies is the inference of enriched biological pathways and protein complexes contained within OMICs datasets. Successful analysis requires the integration of a broad set of current biological databases and the application of a robust analytical pipeline to produce readily interpretable results. Metascape is a web-based portal designed to provide a comprehensive gene list annotation and analysis resource for experimental biologists. In terms of design features, Metascape combines functional enrichment, interactome analysis, gene annotation, and membership search to leverage over 40 independent knowledgebases within one integrated portal. Additionally, it facilitates comparative analyses of datasets across multiple independent and orthogonal experiments. Metascape provides a significantly simplified user experience through a one-click Express Analysis interface to generate interpretable outputs. Taken together, Metascape is an effective and efficient tool for experimental biologists to comprehensively analyze and interpret OMICs-based studies in the big data era.
Highlights
A critical component in the interpretation of systems-level studies is the inference of enriched biological pathways and protein complexes contained within OMICs datasets
Common queries include: What pathways or biochemical complexes are enriched?1; What are the functional roles of identified protein complexes?2; Which candidate proteins are secreted, contain a transmembrane domain, or are otherwise druggable?3; Or are there any chemical probes available for a rapid candidate validation4 ? Critically, when multiple gene lists are analyzed, either from common or orthogonal platforms, the identification of consistent underlying pathways or networks can help decipher authentic signals above the experimental noise[5]
The step-by-step illustration of the Metascape analysis interface for both singleand multiple-list input scenarios are available in Supplementary Figures 1–7. While these examples showcase the analysis of RNAi functional genomics studies, Metascape is capable of analyzing lists of genes from multiple assay types, including transcriptomics, epigenetics, proteomics, and others
Summary
A critical component in the interpretation of systems-level studies is the inference of enriched biological pathways and protein complexes contained within OMICs datasets. In terms of design features, Metascape combines functional enrichment, interactome analysis, gene annotation, and membership search to leverage over 40 independent knowledgebases within one integrated portal It facilitates comparative analyses of datasets across multiple independent and orthogonal experiments. Since each study results in a list containing dozens or hundreds of gene candidates, it is essential to leverage existing biological knowledge through understanding the representation of known pathways or complexes within these datasets Providing this molecular context can facilitate the interpretation of systems-level data and enable new discoveries. The increased accessibility of systems-level technology platforms has promoted experimental strategies that rely on orthogonal OMICs approaches, including transcriptome analysis, genetic screens, and proteomics, to interrogate an experimental system This approach enables a more comprehensive assessment of the molecular features of a biological process and reduces false positive/negative activities associated with individual platforms[9]. This remains a concern to date, as the databases underpinning the interpretation of a majority of published studies are over 2 years old[12]
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